The overarching goal of this Program Project is to advance our understanding of gastric cancer causation utilizing the unique population laboratory identified in Colombia. This Program Project was based at Louisiana State University for 22 years but the activities at that institution were seriously disrupted by Hurricane Katrina in 2005. Since then, the base of operations was transferred to Vanderbilt University in Nashville, TN. This transfer has been highly beneficial for the research because the unique field work opportunities in Colombia are now exploited by an expanded team of scientists whose focus has been Helicobacter pylori infection. The field work in Colombia has continued its highly efficient and economical operation uninterrupted. Three projects and three cores are proposed. Project 1 proposes to continue the long-term follow up of cohorts of adults and children previously treated for Helicobacter pylori infections. It also proposes to study biomarkers of progression, especially DNA methylation, utilizing the tissue bank accumulated over the years. Project 2 addresses the issue of immune modulation by parasites of the response to H. pylori infection, in humans and experimental animals. Project 3 studies oxidative stress induced by Helicobacter isolated from low and high risk populations. Core A provides histopathology services for all projects. Core B deals with all administrative matters and data management. Core C coordinates all field work in Colombia. RELEVANCE: This is one of the few investigations that try to identify the causes of gastric cancer, the second cause of cancer mortality worldwide. The 3 main determinants of such cause are: 1- bacterial infection with Helicobacter pylori;2-immune response to the infection;3- damage to the stomach lining by oxygen radicals.